chr5-81448792-C-T

Variant names:

• chr5-81448792-C-T
• rs371518408
• NM_001256732.3:c.745G>A

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PVS1_Moderate

The NM_001400366.1(SSBP2):​c.720+1G>A variant causes a splice donor, intron change. The variant allele was found at a frequency of 0.000161 in 1,612,472 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000099 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00017 (1 hom.)
• Consequence: SSBP2 NM_001400366.1 splice_donor, intron
• Scores: Splicing: ADA: 0.9526
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.09
• Publications: 0 publications found

Genes affected

SSBP2 (HGNC:15831): (single stranded DNA binding protein 2) This gene encodes a subunit of a protein complex that interacts with single-stranded DNA and is involved in the DNA damage response and maintenance of genome stability. The encoded protein may also play a role in telomere repair. A variant of this gene may be associated with survival in human glioblastoma patients. [provided by RefSeq, Sep 2016]

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PVS1: Splicing +-2 bp (donor or acceptor) variant, product NOT destroyed by NMD, known LOF gene, truncates exone, which is 0.030470913 fraction of the gene. Cryptic splice site detected, with MaxEntScore 8.7, offset of 3, new splice context is: ataGTaagt. Cryptic site results in inframe change. If cryptic site found is not functional and variant results in exon loss, it results in inframe change.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001400366.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SSBP2	NM_001256732.3	MANE Select	c.745G>A	p.Val249Ile	missense splice_region	Exon 11 of 17	NP_001243661.1	A0A087X159
	SSBP2	NM_001394350.1		c.721G>A	p.Val241Ile	missense splice_region	Exon 11 of 18	NP_001381279.1
	SSBP2	NM_001400340.1		c.745G>A	p.Val249Ile	missense splice_region	Exon 11 of 18	NP_001387269.1	A0A087X159

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SSBP2	ENST00000615665.5	TSL:5 MANE Select	c.745G>A	p.Val249Ile	missense splice_region	Exon 11 of 17	ENSP00000483921.1	A0A087X159
	SSBP2	ENST00000320672.9	TSL:1	c.721G>A	p.Val241Ile	missense splice_region	Exon 11 of 17	ENSP00000322977.4	P81877-1
	SSBP2	ENST00000514493.5	TSL:1	c.631G>A	p.Val211Ile	missense splice_region	Exon 10 of 16	ENSP00000426183.1	P81877-4

Frequencies

GnomAD3 genomes AF: 0.0000986 AC: 15 AN: 152138 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000241

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000655

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000191

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000520 AC: 13 AN: 249900 AF XY: 0.0000592

Gnomad AFR exome AF: 0.0000616

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000106

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000168 AC: 245 AN: 1460334 Hom.: 1 Cov.: 30 AF XY: 0.000184 AC XY: 134 AN XY: 726478

African (AFR) AF: 0.0000598 AC: 2 AN: 33430

American (AMR) AF: 0.00 AC: 0 AN: 44448

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26098

East Asian (EAS) AF: 0.00 AC: 0 AN: 39598

South Asian (SAS) AF: 0.00 AC: 0 AN: 85942

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53240

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5762

European-Non Finnish (NFE) AF: 0.000207 AC: 230 AN: 1111474

Other (OTH) AF: 0.000215 AC: 13 AN: 60342

GnomAD4 genome AF: 0.0000986 AC: 15 AN: 152138 Hom.: 0 Cov.: 32 AF XY: 0.0000942 AC XY: 7 AN XY: 74324

African (AFR) AF: 0.0000241 AC: 1 AN: 41428

American (AMR) AF: 0.0000655 AC: 1 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5198

South Asian (SAS) AF: 0.00 AC: 0 AN: 4824

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10596

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.000191 AC: 13 AN: 68022

Other (OTH) AF: 0.00 AC: 0 AN: 2094

Alfa AF: 0.0000974 Hom.: 0

Bravo AF: 0.000121

TwinsUK AF: 0.000270 AC: 1

ALSPAC AF: 0.00 AC: 0

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000116 AC: 1

ExAC AF: 0.0000659 AC: 8

EpiCase AF: 0.000164

EpiControl AF: 0.000119

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Benign	-0.11	T
BayesDel_noAF	Benign	-0.19
CADD	Pathogenic	26
DANN	Uncertain	0.99
DEOGEN2	Benign	0.14	T
Eigen	Uncertain	0.38
Eigen_PC	Uncertain	0.52
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Benign	0.82	T
M_CAP	Benign	0.0052	T
MetaRNN	Benign	0.19	T
MetaSVM	Uncertain	-0.26	T
MutationAssessor	Benign	2.0	M
PhyloP100		6.1
PrimateAI	Uncertain	0.69	T
PROVEAN	Benign	-0.82	N
REVEL	Benign	0.14
Sift	Benign	0.37	T
Sift4G	Benign	0.46	T
Polyphen		0.70	P
Vest4		0.55
MVP		0.15
MPC		0.71
ClinPred		0.073	T
GERP RS		6.0
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.093
gMVP		0.36
Mutation Taster		=70/30	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.95
dbscSNV1_RF	Benign	0.66
SpliceAI score (max)		0.050		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs371518408; hg19: chr5-80744611;